Early effects of cis-dichlorodiammine platinum (II) on tumor progression and programmed death of Ehrlich ascites carcinoma cells

We studied the effects of cis-dichlorodiammine platinum (II) on different pathways of cell death in cultured Ehrlich ascites carcinoma in vitro and on subsequent growth of transplanted tumor in vivo. One-hour incubation with the cytostatic modulated apoptosis in cell culture. However, exposure of cell culture to a minimal effective concentration of cis-platinum(II)diammine dichloride promoted the growth of transplanted tumor.     

Selectivity of angiotensin II antisera

A significant problem in the immunoassay of angiotensin II is the cross-reactivity of most available antisera with the peptide's metabolic products, (des-Asp1)-angiotensin II and (des-Asp1.Arg2)-angiotensin II. In order to attempt to generate antisera of greater selectivity, a variety of conjugates between angiotensin II or derivative peptides and carrier proteins were examined as immunogens with the aim of generating antisera that would selectively identify the amino terminal region of the peptide. Selectivity for the amino terminus was achieved by either (1) immunization with N-acetylated angiotensin II-amide which had been coupled to rabbit serum albumin by its carboxy terminus, or (2) immunization with angiotensin-(1-7)-heptapeptide which was randomly coupled to thyroglobulin. The antisera produced with the N-acetylated immunogen cross-reacted with the unacetylated ligand (Asn1-Val5)-angiotensin, but did not recognize the human hormone (Asp1,Ile5)-angiotensin. Carboxy-terminal coupling of angiotensin without N-acetylation did not induce selectivity for the amino terminus, nor did a conjugate which was linked to the carrier protein via a diazo bond to His6 of the peptide. These findings may be explained by the fact that N-acetylated angiotensin II resists degradation by amino peptidases and thus retains its structure in the immunogen and by the fact that the (1-7)-heptapeptide has lost the immunodominant carboxy-terminal epitope, thus emphasizing the desired amino terminal determinant.     

Glial-vascular reactions to angiotensin II in the rat brain

Reactions of the glia and blood vessels in the sensomotor cortex of adult rats to intraperitoneal injection of angiotensin II were studied electron-microscopically. Repeated injections of the hormone led to edema of increasing severity of the astrocytes, constriction of the lumen of the capillaries, and changes in the structure of their endothelium. It is suggested that these disturbances may be the cause of the cerebrovascular insufficiency and of functional changes in the CNS.Laboratory of Morphology of the Central Nervous System and Laboratory of Experimental Pathology and Therapy of Higher Nervous Activity, Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. S. Rusinov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 615–617, November, 1979.     

Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.     

Amelioration of established murine collagen-induced arthritis with anti-IL-1 treatment.

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis. To validate a key role for IL-1 in arthritic processes we have studied the protective effect of neutralizing antimurine IL-1 antibodies in the murine collagen-induced arthritis (CIA) model. Combination of anti-IL-1 alpha and anti-IL-1 beta given before onset of arthritis was shown to prevent disease completely. Remarkably, a single treatment was also highly effective in the established phase of arthritis, reducing both inflammation as well as cartilage destruction. Suppression was most pronounced with the combination, but anti-IL-1 beta alone also induced significant relief. Finally, we studied the protective effect of IL-1 neutralization on cartilage metabolism in a unilateral expression model of collagen arthritis. To this end zymosan was injected in one knee joint before onset of disease, resulting in accelerated expression in that particular joint and the draining paw. Anti-IL-1 treatment started after accelerated expression of arthritis was able to fully normalize chondrocyte synthetic function, which was highly suppressed in the control group. It is concluded that IL-1 is an important determinant in both inflammation and cartilage destruction in collagen arthritis, and this may have implications for therapy in human arthritis.     

尾加压素II与糖尿病

尾加压素II(urotensin II，UII)最早是从鱼尾部下垂体中分离出的调节肽，近来已从人体中克隆出来，并发现体内一种孤立的G蛋白偶联受体GPR14是其特异性受体。UII与GPR14结合后，参与许多生物学效应，如调节内分泌，调节渗透压平衡，调节胃肠道平滑肌及心血管收缩功能等，是迄今体内最强的缩血管活性肽。UII不仅与许多人类心血管疾病如高血压，充血性心力衰竭（CHF），冠心病和动脉粥样硬化有关，而且研究发现，糖尿病患者血液中UII含量升高。初步研究表明,UII的基因多态性和2型糖尿病的发生有关；尾加压素II还可抑制胰岛素的释放。     

Mucopolysaccharidosis type II (Hunter disease): Identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients

Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT-PCR method. Transient expression in the enzyme-deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45–56 kD) were not detected by Western blot analysis. Further more, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA. © 1995 Wiley-Liss, Inc.     

Microfilamentous type VI collagen in the hyalinized stroma of the hypertrophied ligamentum flavum

Summary Thickened ligamenta flava obtained from 14 patients with spinal canal stenosis were examined with special reference to type VI collagen. The characteristic histological finding in the thickened area was rupture of normal elastic fibre meshwork with resultant fibrosis which usually appeared hyaline. Using an immunohistological method, collagen types VI, I and III were found to be present in the hyaline matrix. Ultrastructural study revealed many microfilamentous structures of type VI collagen admixed in loosely packed, banded collagen fibres. With differential salt precipitation of pepsin-extracted collagen the existence of type VI collagen was confirmed by SDS-polyacrylamide gel electrophoresis analysis and Western blotting analysis using anti-type VI collagen antibody. Quantification of type VI collagen in pepsin-extracted crude collagen samples by an inhibition enzyme-linked immunosorbent assay showed an increasing amount of type VI collagen in the thickened ligamenta flava compared to the normal ligaments. Thus, increase of type VI collagen is the main contribution to the thickening of the ligamentum flavum. This may represent an adaptational and reparative process associated with disruption of elastic fibres.     

Lattices of Type I Collagen Select Invasive Variants of K-ras Oncogene-Transfected NIH3T3 with Less Cellular fibronectin

A clone of NIH3T3 transformant (H3) can yield subcutaneous tumors and experimental pulmonary metastasis in nude mice. Compared to H3 in culture, the cells after in vivo tumor growth (H3-N) acquired enhanced tumorigenicity and metastatic ability. Also, indirect immunofluorescence revealed that cellular fibronectin (c-FN) of H3-N was decreased remarkably. We have studied the interactions between H3 and extracellular matrices to elucidate these phenomena. In the present study, we observed the effect of NIH3T3, H3, and H3-N cultured in type I collagen gel. Morphologically in the collagen gel, NIH3T3 assumed an extensive elongated fiber-like shape, H3 assumed a moderately elongated shape, and H3-N assumed a round or spindle shape with short pseudopodia. Compared to conventional cultures on dishes, cell proliferation of all three types was suppressed in collagen gel, but the degree of the suppression was least in H3-N. As a result, H3-N grew fastest in collagen gel. The variants which acquired growth advantage in the subcutaneum of mice also kept it in collagen gel. H3 cells were cultured in type I collagen gel for 4 weeks, a period comparable to that of tumor formation in nude mice. The cells after this long-term culture (H3-C) acquired enhanced tumorigenicity and metastatic ability nearly equal to that of H3-N. FACS analysis revealed that the c-FN of H3-C had decreased to a value comparable to that of H3-N. This means that type I collagen gel as well as subcutaneous tissues could select variants of H3 with less c-FN through proliferation. Moreover, it is suspected that lattices of type I collagen regulate cell proliferation of fibroblast via c-FN. This revised version was published online in August 2006 with corrections to the Cover Date.